ABSTRACT Our nation?s veterans are at a high risk for developing Chronic Kidney Disease (CKD) with rates of mortality and morbidity that are extremely high. CKD progressing to End Stage Renal Disease (ESRD) is a disabling condition resulting in patients requiring hemodialysis thrice weekly to maintain life. Functional independence on hemodialysis requires a reliable and well-functioning vascular access to connect to the dialysis machine for treatments. Vascular access is crucial to the treatments necessary for hemodialysis patients. Due to their reliability, longevity, and lower complication rates, autogenous arteriovenous fistulas ? surgically created connections between arteries and veins ? have become increasingly prominent over other forms of vascular access. However, the uncertainty associated with fistula maturation has caused undue cost, risk, and stress to patients already undergoing significant medical procedures. Furthermore, fistula dysfunction in the dialysis unit impedes stable effective dialysis, creates undue psychological stress in patients, in addition to increasing the cost of medical care. Currently no system exists to directly and noninvasively measure the underlying causes of vascular remodeling during fistula maturation, or provides comprehensive diagnosis of fistula dysfunction at the bedside. We propose to build and clinically validate an ultrasound diagnostic platform ? referred to as the Point of Care Elastographic Sono-Angiography (eSA) that has unprecedented temporal and spatial resolution to identify vessel wall edges and measure vessel size, elastic properties, and blood-wall shear rate during the cardiac cycles, and 3D mapping of the vascular anatomy at the point of care. After validating this tool both in vitro (through phantom studies on simple and realistic fistula geometries) and in vivo (clinical study conducted on hemodialysis patients pre- and post-fistula creation), we plan to release the software as an open platform tool for researchers. This software tool will be useful for pre-operative planning and post-operative assessment to guide decisions for angioplasty and surgical revision. Given the ubiquity and noninvasive nature of ultrasound imaging and the broad open access with which we plan to release this tool, this proposal can radically accelerate safe and effective ultrasound diagnostic methods for fistula optimization. In addition, given the generalizability to other peripheral vascular systems (carotid, extremities) this system has the potential to optimize vascular diagnostics and thereby improve the functional capacity of veterans suffering from peripheral and cerebral arterial disease. By validating this technology in the dialysis fistula setting, this project will lay the foundation for further clinical research applied to expanded clinical indications in vascular medicine in the future.